Hematopoietic Diseases Flashcards
Where does hematopoiesis occur in the fetus
it begins in the yolk sac and then it shifts to the spleen and liver and then to the fetal bone marrow
T/F Horses release reticulocytes into circulation
F- they do not
What species is the central area of pallor most apparent?
Dogs
What is the mean red blood cell lifespan?
150 days: Horses and cattle
100 days: dogs
70 days: cats
T/F- dogs have a very large storage pool of neutrophils
T
T/F- cats have more marginal neutrophils relative to circulating neutrophils
T- threefold more marginal neutrophils relative to circulating neutrophils
How does the ratio of fat to hematopoietic cells change as an animal matures?
Young age - 25:75 fat to hematopoietic cells
Mid age - 50:50
Old age- 75:25
*Older animals have more fat in their bone marrow
What is the ratio of myeloid to erythroid in normal bone marrow
1:1 but can vary
What areas is hematopoietic marrow concentrated in adults?
spine, pelvis, sternum, ribs, calvarium, and proximal end of limb bones
Where does extramedullary hematopoiesis (EMH) primarily occur in adults?
primarily in the spleen
Extramedullary hematopoiesis (EMH)
the body’s compensatory response to deficient erythropoiesis by the bone marrow or accelerated destruction of erythrocytes and refers to deposits of erythroid precursors in sites other than the bone marrow and peripheral blood.
-Primarily in the spleen
Hematopoiesis
lipolysis + myeloid (bone marrow) expansion in residual red (hematopoietic) marrow
Myelofibrosis
a degenerative change to bone marrow that occurs due to a scar formation after necrosis due to a high concentration of growth factors with marrow injury or activation or idiopathic
causes: leukemias, infiltrative metastatic neoplasia, BVDV, E. canis, FeLV, Sepsis, Drugs or toxins (carprofen, chemo, estrogen, metronidazole, mitotane, phenobarbital, heavy metals)
irradiation
Chronic hemolytic anemia (chronic overstimulation)
What are the infectious agents that can result in myelofibrosis
BVDV
Ehrichia canis
FeLV
Sepsis from infection
What are the 7 causes of myelofibrosis
1) Leukemia
2) Infiltrative metastatic neoplasia
3) Infectious (BVDV, E. canis, FeLV)
4) Sepsis
5) Drugs/ Toxins
6) Irradiation
7) Chronic hemolytic anemia (chronic overstimulation)
What drugs/toxins can result in myelofibrosis?
-Carprofen
-Chemo agents
-Estrogen
-Metronidazole
-Mitotane
-Phenobarbital
-Heavy metals
What is the result to the bone marrow due to emaciation/starvation
Gelatinous transformation (serous atrophy of fat)
Gelatinous transformation
the serous atrophy of fat that occurs die to an animal being starved. Bone marrow is replaced with a mucinous material that shakes like gelatin
What percent of fat in their bone marrow do animals suspected to be starved to death have?
20% residual fat in their bone marrow
you can submit to NDSU Veterinary diagnostic laboratory to confirm the bone marow fat percentage
Disease causes of thrombocytopenia
immune-mediated destruction
hemorrhage
disseminated intravascular coagulation
Disease causes of neutropenia
immune mediated
tissue demand (depends on the storage pool)
What is the stimulus of erythropoiesis and where is it produced
Erythropoietin (produced in the kidney) due to hypoxia
What is the stimulus of thrombopoiesis and where is it produced
Thrombopoietin- produced in the liver and kidney under constant stimulation
Where is thrombopoietin produced
in the liver and kidney under constant stimulation
What is the growth factor for lymphopoiesis of B cells?
IL-4
What is the growth factor for lymphopoiesis of T cells?
IL-2
What is the growth factor for lymphopoiesis of NK cells?
IL-15
Is lymphopoeisis primarily dependent on medullary or extramedullary production
extramedullary production
What are the three ways we can get anemia
1) increased destruction/lysis of RBC
2) Increased loss/hemorrhage
3) Decreased RBC production
Regenerative anemia causes ____________
erythroid hyperplasia in the bone marrow
How does non-regenerative anemia occur
due to a bone marrow insult resulting in erythroid hypoplasia or aplasia in the bone marrow
What are the clinical abnormalities of hemorrhage under regenerative process
1) Chronicity- can have iron deficiency anemia
2) Decreased plasma or serum protein concentration
3) Increased urea nitrogen relative to creatinine
How does blood in upper GI tract result in elevated blood urea?
RBCs are lysed where Hb is absorbed as amino acids.
Amino acids travel in the portal vein to the liver where it is converted into the urea
What are the 4 clinical/pathologic abnormalities of hemolytic anemia under regenerative process
1) Icterus
2) Hyperbilirubinemia (Hb > heme> bilirubin)
3) Hemoglobinuria
4) Splenomegaly (congested in spleen)
What will happen in the bone marrow under regenerative anemia
there will be erythroid hyperplasia as a response
What are 6 causes of non-regenerative anemia?
1) Infectious
2) Toxins/Medications
3) Estrogens
4) Chronic kidney disease (decreased erythropoietin)
5) Iron deficiency (anemia of inflammatory disease)
6) Cancer
Pure Red Cell Aplasia
absence of erythropoiesis and severe non-regenerative anemia
Primary: destruction of early erythroid progenitor cells
Secondary: admin of rhEPO, parvo virus, FeLV subgroup C
Bone marrow: absence of erythroid precursors +/- lyphocytosis, plasmacytosis, thrombocytosis, myeloid hyperplasia
What can result in aplastic anemia in cattle/sheep?
1) Bracken fern
2) Trichloroethylene
what 4 infectious agents can result in aplastic anemia
Ehrlichia (dogs and cats)
Parvovirus (dogs and cats)
FeLV/FIV
Equine Infectious Anemia
What drugs can result in aplastic anemia in dogs/cats
Antimicrobial agents
Chemotherapeutic agents
Estrogen (dogs)
Phenylbutazone (dogs and horses)
What effect does Aflatoxin B have on hematopoeisis
It causes aplastic anemia in horses, cattle, dogs, and pigs
What affect does parvo/ feline panleukopenia virus have on the bone marrow?
Virus has a tropism for mitotically active cells
Oronasal entry to tonsils and Peyer/s patches
Lymphatic spread to the thymus, spleen, and lymph nodes
Virally induced lymphocytosis
Panleukopenia- lymphocytosis in lymphoid tissue and destruction of myeloid precursors in the bone marrow
Immune-mediated neutropenia
immune destruction of neutrophils or their precursors- causes are similar to other immune-mediated cytopenias
Bone marrow: granulocytic hypoplasia or hyperplasia with maturation arrest, aplasia, lymphocytosis and plasmacytosis
Diagnosis of exclusion and response to immunosuppressive therapy
Immune-mediated thrombocytopenia
Often times primarily idiopathic**
Can also be:
-Infectious (EIA, Ehrlichiosis)
-Drug induced (Cephalosporins and sulfonamides)
-Neoplasia
-Other immune mediated diseases
What are the 4 ways you can get an Erythrocytosis?
1) Dehydration (relative)
2) Epinephrine mediated splenic contraction (relative)
3) Epo-mediated eythroid hyperplasia
4) Erythroid neoplasia (uncommon) - polycythemia vera or acute myeloid leukemia-erythroid leukemia
Polycythemia vera
an uncommon chronic erythroid leukemia that results in a marked increased in red cell mass and absence of hypoxemia or other tumors
Normal or decreased plasma erythropoietin concentration
What will the plasma erythropoeitin concentration be in a patient with polycythemia vera
Normal to decreased plasma Epo concentration
Although uncommon, what two erythroid neoplasias can result in erythrocytosis
1) Polycythemia vera (chronic erythroid leukemia)
2) Acute myeloid leukemia- erythroid leukemia
What are the two causes of relative erythrocytosis
1) Water losses (dehydration/ also with increased total protein)
2) Splenic contraction - mostly horses (some dogs)
What are the causes of Secondary Absolute Erythrocytosis
*Stimulated by EPO
1) Hypoxia (Appropriate stimulation)
2) Renal cysts/tumors or liver tumor (inappropriate EPO stimulation)
What is the cause of primary absolute erythrocytosis
*Independent of EPO action
-Polycythemia vera (chronic erythroid leukemia)
What is the cause of persistent lymphocytosis in cattle?
Bovine leukemia virus (a retrovirus)
tropism for B lymphocytes
What are the non-neoplastic causes of lymphocytosis in dogs/cats?
Age/antigenic stimulation (cats)
Epinephrine (cats)
Chronic inflammation
Ehrlichia canis infection
Hypoadrenocorticism (Addisons)
Paraneoplastic lymphcytosis
Hyperthyroidism (cats)
A neoplastic disease originating in the bone marrow- unregulated growth of hematopoietic stem cells
Myeloproliferative disease (common myeloid progenitor cell)
A neoplastic disease of lymphocytes (plasma cells)
includes both lymphoma and leukemia
Lymphoproliferative disease
A diverse group of hematologic disorders characterized by ineffective production of hematopoietic cells
Myelodysplastic syndrome
Myelodysplastic syndrome
clonal myeloid proliferation with ineffective hematopoiesis in the bone marrow resulting in cytopenia of one or more cells line
dysplasia of myeloid (bone marrow) cells
Less than 20% blastocytes in the bone marrow
What infectious disease is associated with myelodysplastic syndrome (dysplasia of myeloid cells due to clonal myeloid proliferation with ineffective hematopoeisis in the bone marrow resulting cytopenia of one or more cell lines
FeLV
Acute Leukemia
Leukemia with an aggressive clinical course (median survival time of 9 days up to 56 days with treatment)
>20% blast cells in the bone marrow
Expression of CD34 antigen by flow cytometry
pancytopenia- anemia, neutropenia, thrombocytopenia
Median age 7-8 years but wide range in dogs
What will the flow results be of a patient with acute leukemia
they will have a CD34+ lymphocytosis
How do you diagnose Chronic Lymphocytic Leukemia in dogs
5000 neoplastic cells/uL
CD8 lymphocytosis (T cell)
CD21 lymphocytosis- CLL/SLL (B cell chronic lymphocytic leukemia/small cell lymphocytic lymphoma)
*Other cytopenias usually not present
What is the most common CLL (Chronic Lymphocytic Leukemia) in cats
CD4 (T cell) lymphocytosis
What are the prognostic factors in dogs with B cell chronic lymphocytic leukemia?
overall median survival time was 300 days (1-1644 days)
Boxers have significant shorter survival time (MST 187)
Non-boxers MST=423 days
High lymphocyte count >60,000 lymph/uL associated with significantly shorter survival
HIgher Ki-67 associated with a worse survival
What breed has a significant shorter survival time for B cell chronic lymphocytic leukemia
Boxers
What is commonly found upon necropsy of an animal with chronic lymphocytic leukemia
-Splenomegaly
-Anemia
-Lymphadenopathy
-High cellular bone marrow
What is commonly found upon necropsy of an animal with acute lymphocytic leukemia
-Pale mucous membranes
-Bone marrow highly cellular but pancytopenia
-Splenomegaly
-Lymph node involvement
-Can infiltrate many organs
What is the importance of flow cytometry in diagnosing lymphoma
-A large number of antigens can be evaluated
-Distinguishes the homogenous from the heterogenous expansions
-Identifies aberrant antigen expression (CD34 expression in acute leukemia)
-Objective measure of size
-Provides prognostic information
Multiple myeloma is a tumor of the ______
plasma cells arising from the bone marrow
Multiple myeloma
a tumor of plasma cells arising from the bone marrow
-markedly increased plasma cells in the bone marrow >30%
-monoclonal gammopathy
-osteolysis from expansion
-light chain proteinuria
Clinical pathology:
-Hyperglobinemia
-Hypercalcemia
-Pancytopenia
Patients with multiple myeloma will have hyperglobinemia. Is this a monoclonalgammopathy of polyclonalgammopathy?
monoclonalgammopathy
What 4 clinical findings will you see with a patient with multiple myeloma
-Hyperglobinemia (monoclonal)
-Hypercalcemia (from osteolysis)
-Pancytopenia
-Light chain proteinuria
What will cytology of a patient with multiple myeloma look like
Tissue is expanded by plasma cells with condensed chromatin, expanded cytoplasm with a perinuclear clear zone
a lentivirus that causes anemia by immune-mediated hemolysis and decreased erythropoiesis resulting in icterus
Equine infectious anemia
What test do you diagnose Equine infectious anemia with?
Coggins Test
How is equine infectious anemia transmitted?
by biting flies
How long does Equine Infectious Anemia last?
it often subsides after a year and horses are lifelong carriers
What are the clinical signs of Equine Infectious Anemia
fever, depression, LN enlargement, splenic congestion, hemolytic crisis characterized by pale with mucosal hemorrhage and dependent edema, increased heart rate
What is your first differential for a horse that presents icteric with rapid breathing and an increased heart rate?
You detect swelling of the limbs
Peteciation of mucous membranes
Splenomegaly upon necropsy
Equine Infectious anemia
Swelling (edema from hemolytic crisis)
Peteciation (hemolytic crisis)
Splenomegaly (hemosiderosis congestion)
What is the causative agent of thrombocytopenic hemorrhagic syndrome in cattle?
Bovine Viral Diarrhea Virus (BVDV)
What CBC abnormalities does BVDV result in?
Thrombocytopenia, Neutropenia, Lymphopenia
Type II infected animals have impaired thrombopoesis (from megakaryocytic necrosis, pyknosis, and degeneration)
severely thrombocytopenic and neutropenic with multisystemic hemorrhagies (GI, spleen, gallbladder, urinary bladder, and LNs)
How does canine distemper virus impact the bone marrow cells?
it causes atrophy and necrosis of bone lining and bone marrow cells (may infect erythrocytes, leukocytes, and platelets
Results in:
Decreased peripheral neutrophils, lymphocytes, mono, platelets during viremia
Thrombocytopenia resulting from mebrane immune complex formation
What CBC abnormalities will you see with distemper virus?
-Neutropenia
-Lymphopenia
-Thrombocytopenia
How does FeLV impact the bone marrow
it disrupts normal hematopoiesis by inducing genetic mutations, infecting hematopoietic cells, dysmyelopoiesis with cytopenias and neoplastic transformation
can be associated with myelodysplastic syndrome
In regenerative anemia would you expect erythroid hyperplasia or hypoplasia in the bone marrow
fill in
When would SPE be used
Serum protein electrophoresis (SPEP) is a test that measures the amount of heavy chain monoclonal protein made by myeloma cells.
Why shouldnt you aspirate or do flow cytometry on a normal adult thymic tissue
There is low cellularity
Where do T cells expand in adult animals?
in the periphery with antigen stimulation
the thymus is replaced by adipose tissue
In a young animal, progenitor cells travel from the bone marrow to the thymus where they are released into the periphery as________
single positive T cells
What is a neoplasm of thymic epithelial cells called?
Thymoma
Flow cytometry on a thymic aspirate of thymoma will reveal what cell population?
How does this differ between the cells in the peripheral blood
Double positive T cells (reactive by neoplastic epithelial cells)
Peripheral blood will be SP and DN t cells (heterogenous) reactive lymphocytosis
What two autoimmune diseases can be paraneoplastic syndromes to thymomas
-Myasthenia gravis (auto-immunity to NMJ)
-Exfoliative dermatitis (auto-immunity to epidermis)
What is spleen function
1) filters blood of foreign material, microorganisms, and removes senescent and altered erythrocytes
2) Reservoir for blood - size and shape can vary markedly
What is function of red pulp of the spleen?
removal, storage, hematopoiesis, phagocytosis (PAMS)
What is the function of white pulp?
Production of B cells and plasma cells to produce antibody and memory lymphocytes
What are periarteriolar lymphoid sheaths
T cells areas that surround the central artery of the white pulp
What cells are in periarteriolar lymphoid sheaths of the white pulp
T cells
What cells are in the splenic follicles of the white pulp
B cells
eccentrically in PALS will form germinal centers when exposed to antigen
Foci can be evident grossly if expanded
What 5 reasons can result in diffuse, soft splenomegaly
*Congestion
1) Gastric volvulus with splenic entrapment
2) Splenic volvulus/torsion
3) Barbiturate euthanasia, anesthesia or sedation
4) Acute hyperemia (septicemia)
5) Acute hemolytic anemia
What is the most common non-neoplastic splenic lesions in dogs, especially in old ones, showing a splenic enlargement
Nodular lymphoid hyperplasia
What infectious agent of cattle and sheep can cause a dark red to black enlarged spleen, containing abundant unclotted blood
Bacillus anthracis (gram +, large, endospore forming bacillus)
Describe the pathogenesis of Bacillus anthracis and its effect on the sheep?
1) Spores are ingested
2) Replicate in the intestinal tract
3) Spread to the lymph nodes
4) Disseminate through bloodstream, causing septicemia
*Splenomegaly (dark to black and contain abundant unclotted blood)
T/F you can see intravascular free Bacillus anthracis in impression smears of the spleen AND peripheral blood
T
What 5 reasons can result in diffuse and firm splenomegaly
1) Marked phagocytosis and proliferation of cells (chronic IMHA)
2) Diffuse granulomatous disease (diffuse or nodular)
3) Extramedullary hematopoiesis (diffuse or nodular)
4) Neoplasia (diffuse or nodular)
5) Storage disease of amyloidosis
What will the texture of the spleen be with amyloidosis
Meaty texture splenomegaly
What will the texture of the spleen be with ImhA
Meaty texture splenomegaly
How do soft bloody nodules occur on the spleen (4 ways)
Due to hemorrhage or congestion
1) Hematomas
2) Incomplete contraction
3) Hemorrhagic infarcts
4) Hemangiosarcoma
A dog presents in lateral recumbency, pale mucous membranes, increased CRT, abdominal fluid wave, and goes into cardiac arrest during examination. Upon necropsy, you notice multifocal dark patches on the lungs, pale adipose tissue, and a dark nodular spleen. What is the likely cause of death?
Hemangiosarcoma
Hemangiosarcomas can commonly metastasize, where are common sites?
to the lung, liver, kidney, and brain
What three breeds are the most commonly diagnosed breeds with Hemangiosarcoma
GlDR, GSHD, and labradors
What are the most common primary sites for hemangiosarcoma to manifest
Spleen, Heart (right auricle), and liver
What structure on the heart is common for hemangiosarcomas to manifest
The right auricle
Hemangiosarcoma is neoplasia of the _________
endothelial cells
Hemangiosarcomas
Neoplasia of the endothelial cells
*Tumors can rupture and cause bleeding into associated cavity
GLDR, GSHD, and labs are the most commonly diagnosed breeds
Weakness, distended abdomen, pale gums, collapse,
most common primary sites: spleen, heart (right auricle), and liver
Metastasis common to lung, liver, kidney, brain
T/F Classic swine fever is eradicated in the US
T- eradicated in the US in 1978
Classic Swine Fever
a highly contagious illness in pigs that varies with strain and immune status of herd
-Pyrexia, Hemorrhages and cyanosis, splenic infarction, infects and injures lymphoid tissue
What affect does classic swine fever have on the spleen
It causes splenic infarction that infects and injures lymphoid tissue (Wedge shapes regions)
additionally hemorrhages and cyanosis
What are the 4 ways you can get firm nodules in the spleen
1) Lymphoid and complex nodular hyperplasia
2) Primary or metastatic neoplasia (can be diffuse)
3) Granulomas or abscessation
4) Extramedullary hematopoiesis
What are the 7 types of primary splenic neoplasia (nodular or diffuse)
1) Splenic stromal sarcoma
2) Histiocytic sarcoma
3) Hemangiosarcoma
4) Lymphoma
5) Myelolipoma
6) Mast cell tumor
7) Plasma cell neoplasia
What are the causes of pyogranulomatous/ granulomatous disease of the spleen?
Bacteria
1) Mycobacteriosis
2) Tularemia
3) Yersiniosis
4) Brucellosis
Fungal
1) Blastomycosis
2) Histoplasmosis
3) Coccidiodosis
4) Sporotrichosis
Protozoa
1) Toxoplasmosis
2) Neosporosis
Viral
1) FIP
Abscesses or pyogranuloma
1) Streptococcous
2) Rhodococcus
3) Trueperella
4) Corynbacterium
*Typically systemic then go to the spleen
What 4 ways can you get soft, bloody, cavitated splenomegaly
1) Hematomas
2) Incomplete contraction
3) Hemorrhagic infarcts
4) hemangiosarcoma
What 4 ways can you get diffuse soft, bloody, cavitated splenomegaly
1) splenic entrapment/volvulus/torsion
2) Barbiturate euthanasia, anesthesia/sedation
3) acute hyperemia/septicemia
4) Acute hemolytic anemia
Splenic mastocytosis (cats)
has cutaneous and visceral forms
Visceral: gastrintestinal and splenic neoplasia
Vomiting, diarrhea, weight loss, and weakness with visceral forms
GI disease associated with a poor prognosis
Splenic disease can have long survival times with splenectomy (metastasis absent)
Histiocytic sarcoma
an interstitial dendritic cell that can arise from many tissues: skin, lung, meninges, lymph node, bone marrow, synovium
Lymph node involvement is common
Can be solidary lesion or multinodular
Common in Bernese Mountain Dogs, Rott, GLDR, and flat coated retrievers
What breed is the poster child for histiocytic sarcomas
Bernese Mountain Dog
What kind of histiocytic sarcoma has the worst prognosis
Hemophagocytic histiocytic sarcoma
macrophages of the spleen and bone marrow
Hemolytic regenerative anemia and thrombocytopenia (coagulopathy)
Diffuse splenomegaly and liver metastasis is common
Accessory spleen
splenic tissue located separately from the anatomical location of the spleen
congenital or acquired
What species are splenic fissures most common in?
Horses
Splenic hemosiderosis
an increased amount of iron in the spleen, usually results from excessive erythrophagocytosis and breakdown of hemoglobin and may be observed in both benign and neoplastic splenic disorders.
Siderotic plaques
rough, brown to yellow plaques along the serosal surface of the spleen
non-neoplastic/incidental
What are the bacterial causes of splenitis
-Mycobacteriosis
-Tularemia
-Yersiniosis
-Brucellosis
Abscesses or pyogranulomas (pyogenic bacteria)
-Streptococcus
-Rhodococcus
-Trueperella
-Corynbacterium
In regard to the thymus, all species have __________ lobes
thoracic lobes
The thymus of ruminants and pigs have ____________ and __________ lobes
Cervical and thoracic lobes
The thymus of cats and horses have _____________ lobes
variable and small cervical lobes
T/F Dogs have a thymus with cervical lobes
F- they only have thoracic lobes
Ruminant thymus has cervical and thoracic lobes with their thoracic lobe being located ________
dorsally
Horse thymus has small cervical lobes (variable number) but their thoracic lobes are located
ventrally
The dog thymus does not have cervical lobes but their thoracic lobe is located ________
ventrally
What species has a thymus with thoracic lobes that are located dorsally
Ruminants
What species have both cervical and thoracic lobes
Ruminants and pigs
What is the cell of origin of a thymoma
epithelial cells
What is the purpose of Hassell’s corpuscles?
they function in the development of a type of T cell that prevents autoimmune responses.
What happens in the subscapular zone of the thymus
T progenitor cells enter from the bone marrow to then enter the cortex for positive and negative selection
What happens in the cortex of the thymus
T cell recognize MHC but not self antigen (Positive selection)
T cell recognize MHC and self antigen (negative selection)
What happens in the medulla of the thymus
5% of the remaining mature T cells leave thymus where they are distributed to the spleen and the lymph nodes
Thymus involution
involution occurs following sexual maturity
-lymphoid and epithelial components are replaced by adipose and connective tissue
-T cells continue to circulate through splenic and lymph node T zones
Antigen-specific T cell expansion occurs with antigen presentation
What happens to the lymphoid and epithelial components when the thymus involutes
It is replaced by adipose and connective tissue
T cells continue to circulate through splenic and lymph node T zones
Thymic hypoplasia
seen in neonatal animals
results in immunodeficiency
Thymic atrophy/necrosis
due to lymphocytolysis or inadequate supply from the bone marrow
-heavy metals, radiation, anti-cancer therapy, fungal toxins, viral disease
How can we get thymic atrophic or necrosis
heavy metals, radiation, anti-cancer therapy, fungal toxins, viral disease
Name 6 viruses that affect the thymus
1) Parvovirus (dogs and cats) -injury lymphoid tissue/necrosis
2) Canine distemper virus-injure lymphoid tissue
3) FIV - injure lymphoid tissue
4) Equine Herpes-Virus-1- injure lymphoid tissue
5) BVDV - injure lymphoid tissue
6) Porcine circovirus-2 -inflammation of the thymus
What are 5 broad reasons for thymic enlargement in an adult
1) Hemorrhage
2) Inflammation
3) Neoplasia
4) Cysts
5) Hyperplasia
How might thymic hemorrhage occur
-Anticoagulants (rodenticide toxicity)
-Trauma
-Idiopathic/spontaneous
What causes multisystemic wasting syndrome in pigs
Porcine circovirus-2
What virus causes:
-Enlarged lymph nodes, interstitial pneumonia, and poor body condition
Thymus atrophy to granulomatous inflammation with multinucleated cells with cytoplasmic viral inclusions
Porcine circovirus-2 (Post-weaning multisystemic wasting syndrome)
What are your four top differentials for a mediastinal mass identified radiographically?
1) Thymoma
2) Lymphoma
3) Hemangiosarcoma
4) Neuroendocrine tumor
What are 3 paraneoplastic syndromes associated with thymoma
1) Myasethenia gravis and megaesophagus (up to 40%)
2) Thymoma associated lymphocytosis
3) Exfoliative dermatitis- ulceration and scaling; individual epithelial cell necrosis
T/F BLV in cattle is associated with thymic lymphoma
False
Where are the T cells concentrated in a normal lymph node?
the paracortex
Where are the B cells concentrated in a normal lymph node?
the germinal centers (cortex) - B cells react to antigen and produce AB
What are of the lymph node do you have plasma cells and macrophages
the medulla
stimulated node cords are filled with antibody secreting plasma cells
Sinus histocytes on meshwork and phagocytize foreign material, cell debris, and bacteria
How do the majority of lymphocytes enter the lymph node?
through high endothelial venues (HEV)
afferent lymphatic vessels in capsule and drain to sinuses
Exit at hilus efferent lymph vessel
How do lymphocytes exit the lymph node
they exit at the hilus efferent lymph vessel
what vessels enter lymph nodes
afferent lymphatic vessels
lymphocenter
a group of nodes present in the same location and drain the same region
Mesenteric lymphagiectasia
is a disorder characterized by dilation, obstruction, and/or dysfunction of the lymphatic vessels within the small intestine. Dogs with IL often suffer from diarrhea, weight loss, vomiting, and fluid accumulations secondary to protein loss from the intestine
Enteric lymphangiectasia
caused by dilated lymphatics +/- obstructed or inflammated lymphatics
Diffuse, segmental, focal
Villous expansion by lacteal dilation (white spots)
Present with Chronic GI signs, fluid accumulation
What is the most common cause of enteric lymphangiectasia?
Protein losing enteropathy- resulting in hypoproteinemia, hypocholesterolemia, lymphopenia, hypocalcemia
Intestinal lipogranulomatous lymphangitis
inflammatory foreign body reaction to lipid-rich chyle
Chronic GI signs
focal or multifocal
White micronodules on the serosa of intestine and mesenteric fat
No PLE at presentatio n
What breeds are most likely to have intestinal lymphangiectasia
Yorkshire Terriers
Norwegian Lundehund
You have a Yorkshire terrier that presents with chronic diarrhea, wasting, hypoproteinemia, lymphopenia, hypocalcemia and hypocholesterolemia
Peripheral edema, ascites, hydrothorax
What is the likely diagnosis
Enteric lymphangiectasia
Enteric lymphangiectasia, a protein-losing enteropathy. What else can also cause this?
-Lymphatic obstruction
-Increased lymphatic pressure due to inflammation
-Neoplasia
-Granulomatous infiltrates
Lymphangiosarcoma
neoplasia of lymphatic endothelium
Clinical signs: pitting edema, mass/swelling cervical trunk or limb
multimodal therapy (sx and chemotherapy)
What are the clinical signs of lymphangiosarcoma
pitting edema
mass.swelling cervical trunk or limb
What are the causes of chylothorax
idiopathic
trauma
congestive heart failure (more common in cats)
chest tumors
What are the clinical signs of chylothorax
-Difficulty breathing
-Coughing
-Difficult to auscultate the chest
-Atelectasis
-Can have lymphopenia due to loss of lymphocytes in the fluid
What is lymphoid tissue that doesnt have a node but can react when it comes across antigen
MALT, BALT, GALT
tonsils, nasal cavity, conjunctiva, and urinary plater
What do M cells found in the peyer’s patches do?
They deliver antigen to dendritic cells > peyer’s patches/MALT
Peyer’s patches are overlaid by _________________ with numerous ___________ cells
follicle-associated epithelium with numerous M cells
What are some bacteria that gain entery through M cells located in the Peyer’s patch
Salmonella, Listeria, Mycobacterium, and Yersinia
Hemal nodes
prominent in ruminants but also in horses and primate
Sinuses filled with blood “miniature spleen” can filter blood and remove senescent erythrocytes
What is present in ruminants, horses, and primates to function as a min spleen to filter blood and remove senescent erythrocytes
Hemal nodes
What 6 reasons might cause lymph nodes to atrophy?
1) Primary immunodeficiency disease
2) Lack of antigenic stimulation
3) Viral infection
4) Cachexia and malnutriton
5) aging
6) Radiation
What viral diseases can cause lymphoid injury?
1) Parvovirus
2) Distemper
3) FIV
4) Equine Herpes-1 Virus
5) BVDV
Why are the mesenteric and oral nodes normally larger
because they are processing antigens and bacteria from the intestinal tract
lymphofollicular hyperplasia
might be in pathology report
numerous prominent secondary follicles
Paracortical hyperplasia
might be in pathology report
expansion of the paracortex
Sinus histiocytosis
might be in pathology report
increased histocytes in the sinuses of the lymph node
Sinus hemosiderosis
might be in pathology report
increased hemosiderin laden macrophages and erythrophagocytosis
Sinus edema or erythrocytosis
might be in pathology report
expanded sinuses of the lymph node by edema or red blood cells
acute lymphadenitis
results in lymphadenomegaly
affects lymph nodes draining the sites of infection
Red and edematous can have taut capsule, necrosis and lymphangitis
culture for bacteria, examine impression smears for bacteria, histopathology
Culture for bacteria, examine impression smears for bacteria, histopath
What are differentials for a cat with peripheral lymphadenomegaly
-Lymphoma (not as common as cats, dogs have multinodal commonly)
-FIV
-Dental disease
-Immunization
-Bartonella
-Yersinia pestis
-Tularemia
Yersinia pestis
a gran negative coccobacillus that is carried in the fleas of squirrels, praire dogs, rabbits, and woodrats
transmitted when eating an infected animal or bitten by an infected flea
Signs: pyrexia, loss of appetite, lethargy, enlarged lymph nodes
Need to start treatment early
Zoonotic
What form of plague is transmitted through fleas/rodents?
The bubonic form- fever, headache, and swollen lymph nodes
What form of the plague is transmitted through the skin
the septicemic form- fever, shock, and hemorrhage
What form of the plague is transmitted through air droplets
Pneumonic form- fever, headache, and pneumonia
What are the infectious causes of lymphadenitis
1) Yersinia pestis
2) Mycobacterium avium ssp paratuberculosis
3) Rhodococcus equi ssp. Equi
4) Histoplasmosis
What causes Strangles in horses
Streptococcus equi ssp. Equi
-highly contagious
Describe the pathogenesis of Strangles
1) Inhalation
2) Retropharyngeal and submandibular enlargement from LN abscesses
3) compress pharynx
4) ruptured abscess may spread blood or lymph to other organs
*Purpura hemorrhagica (hypersensitivity III, may result in necrotizing vasculitis with repeated exposure)
Bastard Stangles
wen abscesses from Streptococcus equi ssp. equi ruptures and spread blood or lymph to other organs
Purpura hemorrhagica
a type III hypersensitivity that occurs through multiple exposures to Streptococcus equ ssp. Equi
causes a necrotizing vasculitis
Rhodococcus equi
affects foals up to 6 months of age. causes bronchopneumonia but 50% of foals can develop a pyogranulomatous ulcerative enterotyphlocoloties of the Peyer’s patches
50% of foals with Rhodococcus equi can also develop what, in addition to the bronchopneumonia
Pyogranulomatous lymphadenitis of the mesenteric and colic lymph nodes
A buffalo presents for necropsy. animal showed chronic wasting, intestine had a thickened mucosa
on histopath you see aggregates of epithelioid macrophages and multinucleated giant cells. There were acif-fast staining bacilli within epithelioid macrophages. What is the cause?
Johne’s disease (mycobacterium avium paratuberculosis)
What is the causative agent of Johne’s disease
Mycobacterium avium paratuberculosis
causes enteritis and granulomatous lymphadentitis
How would you identify Mycobacterium avium paratuberculosis on histopath
they are acid fast and within the macrophages
Sheep and goats with Johne’s disease may have
granulomas with necrotic caseous centers and mineralization
Mycobacterium bovis
bovine tuberculosis- lymph nodes are necrotic and suppurative/abscessed
chronic progressive disease
humans infected by consuming raw milk or milk products
sheep presents with an abscess that is encapsulated and contains greenish thick, opaque fluid
mandibular lymph nod is enlarged. the contents are thick and inspissated and tan to white
Caseous lymphadentitis
Corynebacterium
What can cause lymphoid depletion with granulomatous inflammation with multinucleated giant cells and cytoplasmic inclusion bodies
Porcine circovirus -2
Postweaning multisystemic wasting syndrome
Porcine reproductive and respiratory syndrome virus (PRRS)
an arterivirus with a predilection for lymphoid tissues
Virus replicates in the macrophages of lymphoid tissues and lungs and may persist in tonsil and lung macrophages
Reduced phagocytic and function of macrophages
Intersititial pneumonia and generalized lymphadenopathy, tracheobronchial and mediastinal most commonly affected
Lymph nodes can be hemorrhagic or enlarged pale tan +/ cystic and firm
Where does procine reproductive anf respiratory syndrome virus replicate
it replicates in macrophages of lymphoid tissues and lungs and may persist in tonsil and lung macrophages
-causes interstitial pneumonia and generalized lymphadenopathy
Name an arterivirus with predilection for lymphoid tissues
Porcine reproductive and respiratory syndrome virus (PRRS)
A histiocyte in the skin is called a
Langerhans cell
a histiocyte in the tissue is called a
Macrophage
What is the cellular origin of hemophagocytic histiocytic sarcoma
splenic macrophage
What are the 4 categories that define the types of lyphoma
1) Anatomic location (multcentric, alimentary, mediastinal/thymic, spleen, cutaneous, etc)
2) Cellular origin: B lymphocyte vs T lymphocyte vs precursor
3) Histologic pattern- diffuse vs nodular
4) Biologic behavior (indolent-low grade to aggressive-high grade)
What are the clinical signs of lymphoma
-Generalized lymphadenomegaly
-Thickened intestine, hepatomegaly, splenomegaly
-Advanced disease (aspiration of bone marrow, spleen, liver and LNs)
-Mild to moderate nonregenerative anemia is common
-Lymphopenia/lymphocytosis
-Hypercalcemia (mediastinal involvement)
-Hyperglobulinemia
An excellent non-invasive method for peripheral lymphadenopathy and suspicion of lymphoma
typically need a significant neoplastic population within the sample
Cells must be viable
Samples include fresh peripheral blood, lymph node, and tissue aspirates
Some types of lymphoid neoplasia need histopathology for subtyping
Flow Cytometry
T/F Cytology can provide a lymphoma diagnosis but cannot subtype lymphoma
T
What thickness of tissue is needed for lymph node biopsy
at least 2mm thickness to assess tissue architectural
avoid compression of tissue (crush artifact)
Why is it important to promptly transfer the tissue to the fixative when doing a lymph node biopsy
mitotic activity can be up to 40% decreased with mroe than 12 hour delay
PARR
Can use a variety of different sample types (old or non-viable flow sample)
Diagnosis: distinguish between neoplasia and hyperplasia/reactive process, sensitive in a sample without a significant neoplastic process, no prognostic information
T/F PARR tells you diagnosis but does not tell you prognosis
True
T/F Both Flow Cytometry and PARR samples need to be viable
Only Flow Cytometry samples need to be viable
PARR samples do not need to be viable
What are the different types of lymphoma in dogs?
-Multicentric: Diffuse large B cell is most common (Also Small B cell (MZL/DSBCL/FL) and PTCL, TZL)
-Enteric lymphoma: (T cell origin, small and large) and (Colonic large B cell)
-Cutaneous lymphoma: Cutaneous epitheliotropic T cell lymphoma most common
-Thymic lymphoma: T cell most common, Acute lekemia and PTCL can have mediastinal involvement
-Splenic lymphoma: Splenic marginal zone lymphoma are most common
Which of the dog lymphomas can typically be diagnosed by flow cytometry
1) Multicentric lymphoma: Diffuse large B cell, Small B cell, PTCL, TZL
2) Thymic lymphoma: T cell, Acute leukemia and PTCL can have mediastinal involvement
What is the most common type of lymphoma in cats
Enteric lymphoma
1) Small mucosal epitheliotropic T cell lymphoma- small intestine - good prognosis of 28 months
2) Large T cell transmural (poor)
3) Large B cell in stomach and large intestine (poor)
Thymic lymphomas in cats are often associated with _________
FeLV or FIV
How can histologic grade help to predict the outcome of feline intestinal T cell lymphoma
Transmural or Mucosal (Transmural = worst prognosis with lower survival probability)
Cell size (Large= worst prognosis with lower survival probability)
Generally speaking: does large cell or small cell feline intestinal T cell lymphoma have a worst prognosis
Large cell
What is the most common lymphoma in horses
T ell rich large B cell lymphoma- cutaneous
In horses, GI lymphoma can also cause____________
a wasting syndrome
What is the most common neoplasia in pigs
Lymphoma
(Females > Males)
What is the most common kind of lymphoma in pigs
Multicentric visceral lymphadenopathy
What is the most common lymphoma in goats
Mostly multicentric with involvement of thymus, liver, kidney and lung
T cell is more common than B cell
Merek’s Disease
a gallid alphaherpes virus 2 that is highly contagious
matures in the feather follicle
enlarged peripheral nerves
diffuse or nodular lymphoid tumors
commonly present with unilateral paralysis
tumors can develop in heart, ovary, liver, lung, kidney, eyes, feather follicles, nervous system
Lymphoid leukosis in chickens
a retrovirus that caused nodular lymphoid tumors
Bursa of Fabricus usually involved
What infectious disease causes lymphoma and affects the bursa of fabricus
Lymphoid leukosis
What infectious diseases causes enlarged peripheral nerves and diffuse or nodular lymphoid tumors in chickens
Mereck’s disease (gallid alphaherpes virus 2)
How do patients with Mareck’s disease typically present?
with unilateral paralysis
What is the phenotype of Bovine enzootic lymphoma caused by bovine leukosis virus (BLV)
B cell lymphoma
What percent of cattle with bovine leukosis virus will develop lymphoma
Less than 5% of cattle
(30% will have a non-neoplastic persistent lymphocytosis)
BLV associated lymphoma is more common in what kind of cattle
Adult dairy cattle
BLV associated lymphoma
B cell phenotype
30% have non-neoplastic persistent lymphocytosis
5% infected will develop lymphoma
More common in adult dairy cattle
Common sites: lymph nodes, abomasum, uterus, and heart (HULA), other sites include retro-oribtal, renal and spinal cord, stomach
Lymphoma (non-BLV associated) in cattle has what three components?
1) Thymic disease (<2 years of age): Respiratory distress
2) Multicentric disease (3-6 months old): liver, spleen, kidney, BM involvement
3) Cutaneous (1-3 years old)- plaques
How do carcinomas typically metastasize?
to regional lymph nodes through the lymphatic cells
Mast cell tumors and malignant melanomas are frequently metastatic to _____________
lymph nodes
How do sarcomas typically metastasize?
hematogenous
When is the PARR assay most useful?
When previous findings are concerning for lymphoid neoplasia but not definitive
What disease is multicentric lymphoma associated with in cats?
FeLV or FIV
A sheep presents with an enlarged lymph node or a mass in the cervical region. There are multiple animals with similar lesions on the farm. On cytology there are neutrophils with intracellular bacteria. What bacteria are you most concerned about.
Corynebacterium pseudotuberculosis
What features are prognostic in feline intestinal lymphoma?
Transmural versus mucosal involvement
B cell versus T cell
Cell size of T cell lymphoma
